Colchicine acts as a potent anti-mitotic agent in both normal and tumor cells. It is the object of the proposed research to design and prepare selective and irreversible antimitotic agents, derived from colchicine, as antitumor agents. This is to be accomplished bydeterming the structural features of colchicine involved in binding to microtubule protein of te spindle and the nature of th areas on the protein adjacent to the binding site, and finally by using this information to design derivatives bearing functional groups capable of vovalent bond formation with the protein outside the binding site. This last aspect will take advantage of the fact that the protein may vary in its amino acid make-up outside the binding site without changeing its affinity for colchicine or its abili y to function in microtubule formation. Mouse brain will serve as the source of non-tumor microtubule protein while murine neuroblastoma will be used to obtain microtubuleprotein of neoplastic origin. Each compound will be tested for antimitotic activity in cell culture using L-929 mouse fibroblasts. This information will indicate whether there is a correlation between microtubule binding and antimitotic activity.